TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin.
Although DNA double-strand break (DSB) repair is mediated by numerous proteins accumulated at DSB sites, how DNA repair proteins are assembled into damaged chromatin has not been fully elucidated. Here we show that a member of the tripartite motif protein family, TRIM29, is a histone-binding protein responsible for DNA damage ... response (DDR). We found that TRIM29 interacts with BRCA1-associated surveillance complex, cohesion, DNA-PKcs and components of TIP60 complex. The dynamics of the TRIM29-containing complex on H2AX nucleosomes is coordinated by a cross-talk between histone modifications. TRIM29 binds to modified histone H3 and H4 tails in the context of nucleosomes. Furthermore, chromatin binding of TRIM29 is required for the phosphorylation of H2AX and cell viability in response to ionizing radiation. Our results suggest that TRIM29 functions as a scaffold protein to assemble DNA repair proteins into chromatin followed by efficient activation of DDR.
Mesh Terms:
Cell Survival, Chromatin, DNA Damage, DNA Repair Enzymes, DNA-Binding Proteins, HEK293 Cells, HeLa Cells, Histone Acetyltransferases, Histones, Homeodomain Proteins, Humans, Immunoprecipitation, In Vitro Techniques, Lysine Acetyltransferase 5, Mass Spectrometry, MutS Homolog 2 Protein, Nucleosomes, Repressor Proteins, Transcription Factors, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases
Cell Survival, Chromatin, DNA Damage, DNA Repair Enzymes, DNA-Binding Proteins, HEK293 Cells, HeLa Cells, Histone Acetyltransferases, Histones, Homeodomain Proteins, Humans, Immunoprecipitation, In Vitro Techniques, Lysine Acetyltransferase 5, Mass Spectrometry, MutS Homolog 2 Protein, Nucleosomes, Repressor Proteins, Transcription Factors, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases
Nat Commun
Date: Jun. 22, 2015
PubMed ID: 26095369
View in: Pubmed Google Scholar
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